Abstract

Both gene expression levels and eQTLs (expression quantitative trait loci) are partially tissue specific, complicating the detection of eQTLs in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be non-trivial, allowing for inference of eQTL functioning in the brain via eQTLs measured in readily accessible tissues, e.g. whole blood. Using Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantify the enrichment of blood and brain eQTLs in genome-wide association study (GWAS) for three immune-related traits (Crohn′s disease, rheumatoid arthritis, and ulcerative colitis), three brain-related (BMI, educational attainment, and schizophrenia), and five traits not associated with either tissue. Our analyses establish strong enrichments of blood (32-113 fold enrichment, mean=59) and brain (21-63 fold enrichment, mean=40) eQTLs in their effects across all traits. We find no evidence for tissue-specific enrichment in GWAS signal for either eQTLs uniquely found in the brain or whole blood. To extend our finding, we test tissue-specific enrichment of eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium, and, again, find no tissue-specific eQTL effects. Finally, we integrate the GTEx eQTLs with tissue-specific epigenetic data and find substantially enriched effects on schizophrenia, though again not tissue specific. We conclude that, while eQTLs are strongly enriched in GWAS, the enrichment is not specific to the tissue used in eQTL discovery. Therefore, using relatively accessible tissues, such as whole blood, as proxy for eQTL discovery is sensible; and restricting lookups for GWAS hits to a specific tissue might not be advisable.